Thyroid disorders are among the most common endocrinological diseases. Hypothyroidism, in which the thyroid glands produce too little hormone, can reduce the metabolic rate to as low as half the normal rate, while hyperthyroidism, in which an excess of thyroid hormone is produced, can double it. Between 8 and 9 million Americans suffer from hypothyroidism and its associated diseases, which include Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) which affects 1 out of 5 women over the age of 75, nontoxic goiter (iodine deficiencies), neonatal goiter (cretinism), and Riedel's thyroiditis. Approximately 350,000 Americans suffer from hyperthyroidism in the form of Grave's disease (toxic goiters or thyrotoxicosis), toxic nodular goiter, neonatal hyperthyroidism, and iatrogenic hyperthyroidism.
Methods for the detection of thyroid disorders utilize several species in the bloodstream as biological markers whose levels are measured as an indication of the presence and type of disorder. Triiuodothyronine (T3) and thyroxine (T4) are two of the markers. In conditions of hypothyroidism, the levels of these markers, which are normally within the ranges of 1.1-2.9 nmol/L and 64-142 nmol/L in serum, respectively, are low, while in conditions of hyperthyroidism they are elevated. Another marker, thyroid stimulating hormone (TSH), varies in the opposite direction by being elevated in conditions of hypothyroidism and depressed in conditions of hyperthyroidism, both relative to a normal serum level of 0.5-5 mIU/L. In certain conditions, notably Hashimoto's thyroiditis, anti-thyroglobulin (anti-Tg) antibodies and anti-thyroid peroxidase (anti-TPO) antibodies (the latter also referred to as antimicrosomal antibodies), which are additional markers, are also elevated, although an anti-TPO determination without an anti-Tg determination is often considered adequate. Other tests include measurements of the basal metabolic rate and closed percutaneous biopsies of the thyroid.
To diagnose a thyroid disorder by serum analyses, the physician thus needs to detect the levels of either four or five markers. Using an individual procedure for each marker can be an expensive undertaking in terms of materials, equipment, and labor, and the risk of error is proportional to the number of procedures performed. By contrast, if the physician can detect all of the markers in a single test, the cost would be less, the probability of error would be significantly decreased, and the risk of the need for a repeat test (and the awkwardness of requesting an additional blood sample from the patient) would be lessened. In addition, the time involved in diagnosis, treatment, and recovery may be substantially reduced.
Unfortunately, the development of a unified or simultaneous test procedure has thus far been discouraged by the technology required to perform multianalyte analyses and by differences among the properties of the particular markers. Some but not all of the markers are antibodies, some are small molecules and others large, and some are present in lower concentrations than others and therefore require assays of greater sensitivity. While each can be detected by an immunoassay of some kind, the chemistries of the immunoassay differ from one analyte to the next, and different reagents are added at different times. It is indeed a challenge to accommodate these differences and produce an assay that can provide individual values for each of the markers and yet be performed in a single reaction mixture.